Screening of photosensitizers-ATP binding cassette(ABC)transporter interactions in vitro  

作　　者：Shruti Vig Payal Srivastava Idrisa Rahman Renee Jaranson Anika Dasgupta Robert Perttilä Petteri Uusimaa Huang-Chiao Huang 

机构地区：[1]Fischell Department of Bioengineering,University of Maryland,College Park,MD 20742,USA [2]Laboratory of Cell Biology,Center for Cancer Research,National Cancer Institute,National Institutes of Health,Bethesda,MD 20892,USA [3]Modulight Corporation,Tampere FI-33720,Finland

出　　处：《Cancer Drug Resistance》2024年第1期382-402,共21页癌症耐药(英文)

基　　金：support from the US NIH Trailblazer Award(NIBIB R21EB028508);US National Science Foundation(CBET-2030253,CBET-2037815);the US NIH(R01CA260340,R01CA256710);Modulight Corporation;I.R.is supported by the NCI-UMD partnership for integrative cancer research fellowship;Rahman I and Dasgupta A are supported by the University of Maryland ASPIRE Fellowship;Vig S is supported by the MPower Fellowship.

摘　　要：Aim:ATP-binding cassette(ABC)transporters are proteins responsible for the efflux of drug molecules from cancer cells,reducing the efficacy of anti-cancer treatments.This study assesses the susceptibility of a panel of clinically used photosensitizers to be transported by ABC transporters in vitro.Methods:The involvement of P-glycoprotein(P-gp/ABCB1),breast cancer resistance protein(BCRP/ABCG2),and multidrug resistance-associated protein 1(MRP1/ABCC1)in the transport of 7 clinically utilized photosensitizers[benzoporphyrin derivative(BPD),temoporfin,redaporfin,talaporfin sodium,rose bengal,methylene blue,and indocyanine green]were investigated using human breast cancer cell lines following well-established protocols.Briefly,parental MCF-7 cells and sublines that overexpress P-gp(MCF-7 TX400),ABCG2(MCF-7 MX100),or MRP1(MCF-7/VP)were treated with photosensitizers with and without ABC transporter inhibitors.Intracellular levels of photosensitizers were measured using extraction method and flow cytometry to determine whether the ABC transporters are associated with efflux or uptake of photosensitizers.Results:The ABCG2 inhibitor(fumitremorgin C)and P-gp inhibitor(valspodar)effectively blocked the transport mediated by ABCG2 and P-gp of rose bengal and BPD.Redaporfin showed increased accumulation in the presence of valspodar with flow cytometry.Interestingly,MCF-7/VP cells were found to have reduced intracellular accumulation of rose bengal,which was restored with MRP1 inhibitor(MK571).The cell viability assay showed photodynamic therapy(PDT)resistance with Redaporfin in P-gp-overexpressing cells,BPD in ABCG2-and P-gp-overexpressing cells,and with Rose bengal in ABCG2-,P-gp-and MRP1-overexpressing cells,respectively.However,no change in intracellular retention was observed for other photosensitizers.Conclusion:In summary,our study provided new knowledge that temoporfin,talaporfin sodium,methylene blue,and indocyanine green are not substrates of ABCG2,P-gp,or MRP1.Redaporfin is a substrate for P-gp.BPD is a known subst

关 键 词：Multidrug resistance ATP-binding cassette(ABC)transporters PHOTOSENSITIZERS photodynamic therapy 

分 类 号：R73[医药卫生—肿瘤]